In the cortex, synapses occur in places where the postsynaptic dendritic branch are within the reach of a dendritic spine to a presynaptic axon terminal. The average spine length is around 2 μm; 1.8 in the CA1 / CA3 and 2.6 in V1 (see here). Regions in which this distance is small enough to conceivably make a connection are called “potential synapses.”
Synaptic connectivity between nearby neurons is somewhat rare. Thomson and Lamy call this connectivity the “hit rate” and estimated it in a bunch of different neuron types (see their awesome table here). They estimate hit rates ranging from ~ 0.01 to ~ 0.7 depending on neuron class, with a rough average of about 0.25.
However, most neuron combos that have any synapses have several synapses, which we wouldn’t expect from such a low hit rate if their formation was independent. And indeed, this aberrantly high proportional of multiple synapses holds true even after adjusting for synaptic compatibility.
Fares and Stepanyants propose a model of cooperativity. Connections with a number of synapses that exceed an adjustable critical number of synapses are stabilized, whereas connections with fewer than this number of synapses are degraded. Here is evidence that their model (green) can fit experimental data (red bars) of synapses from rat barrel cortex:
The authors speculate that the cooperativity may be mediated by competition among axons for connections to a given dendritic branch. The total number of connections along a dendritic branch could be regulated homeostatically such that if one connection forms another must be eliminated. Along with their critical number of synapses threshold, this would lead to positive feedback effects following to the formation of one synapse.
One note: Fares’s study only looked at synaptic connections of less than 50 μm, while most synapses are actually the result of longer-range connections.
Fares T, et al. 2009 Cooperative synapse formation in the neocortex. PNAS doi: 10.1073/pnas.0813265106
Thomson AM, et al. 2008 Functional Maps of Neocortical Local Circuitry. doi: 10.3389/neuro.01.1.1.002.2007